Related Experiment Video

Updated: Jul 13, 2025

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling
10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

18.3K

Tetracyclines activate mitoribosome quality control and reduce ER stress to promote cell survival

Conor T Ronayne1,2, Thomas D Jackson1,2, Christopher F Bennett1,2

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

EMBO Reports
|October 11, 2023
PubMed

Insights

Tetracyclines inhibit mitochondrial translation and promote cell survival by suppressing endoplasmic reticulum stress. This involves the mitoribosome quality control factor MALSU1, revealing a new survival pathway for mitochondrial diseases.

Area of Science:

  • Cell Biology
  • Genetics
  • Biochemistry

Background:

  • Mitochondrial diseases stem from oxidative phosphorylation defects due to gene mutations.
  • Cellular phenotypes include redox imbalances and inflammation, leading to cell death vulnerability.
  • Tetracyclines can inhibit mitochondrial translation and rescue this vulnerability, but mechanisms are unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which tetracyclines promote cell survival in mitochondrial disease contexts.
  • To investigate the role of endoplasmic reticulum (ER) stress in tetracycline-mediated cell protection.

Main Methods:

  • Investigated tetracycline effects on mitochondrial translation and ribosome function.
  • Assessed the role of the mitoribosome quality control factor MALSU1.
  • Examined the impact of tetracyclines on ER stress pathways, including the unfolded protein response and IRE1α signaling.
  • Utilized glucose starvation models to induce ER stress.

Main Results:

  • Tetracyclines inhibit the mitochondrial ribosome, promoting cell survival.
  • Tetracyclines increase mitochondrial MALSU1 levels and its recruitment to the large mitoribosome subunit.
  • MALSU1 is essential for tetracycline-induced survival and ER stress suppression.
  • Tetracyclines inhibit glucose starvation-induced ER stress and IRE1α-mediated cell death.

Conclusions:

  • Tetracycline treatment establishes a novel interorganelle communication pathway from the mitoribosome to the ER, promoting cell survival.
  • This mechanism involves MALSU1 and offers a new therapeutic strategy for mitochondrial diseases.
  • Understanding this pathway sheds light on fundamental cell survival mechanisms.
Keywords:
IRE1αMALSU1mitochondrial diseasemitoribosometetracyclines

More Related Videos

Rapid Isolation of the Mitoribosome from HEK Cells09:33

Rapid Isolation of the Mitoribosome from HEK Cells

Published on: October 4, 2018

11.1K
Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae09:05

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

29.1K

Related Concept Videos

Stringent Response in E. coli01:23

Stringent Response in E. coli

Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
17
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
20
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.5K